Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana.

OBJECTIVES: Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial. DESIGN: Cluster-randomised controlled trial. SETTING: Rural Ghana PARTICIPANTS: 1943 children (6-35 months of age) with geocoded compounds. INTERVENTIONS: Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron. PRIMARY AND SECONDARY OUTCOME MEASURES: Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention. RESULTS: The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined. CONCLUSION: In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT01001871.

Effect of iron fortification on malaria incidence in infants and young children in Ghana: a randomized trial.

IMPORTANCE: In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies. In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas. OBJECTIVE: To determine the effect of providing a micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, cluster randomized trial of children aged 6 to 35 months (n = 1958 living in 1552 clusters) conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia (hemoglobin level <7 g/dL), or severe wasting (weight-for-length z score <-3). INTERVENTIONS: Children were randomized by cluster to receive a MNP with iron (iron group; 12.5 mg/d of iron) or without iron (no iron group). The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated. MAIN OUTCOMES AND MEASURES: Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period. RESULTS: In intention-to-treat analyses, malaria incidence overall was significantly lower in the iron group compared with the no iron group (76.1 and 86.1 episodes/100 child-years, respectively; risk ratio (RR), 0.87 [95% CI, 0.79-0.97]), and during the intervention period (79.4 and 90.7 episodes/100 child-years, respectively; RR, 0.87 [95% CI, 0.78-0.96]). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (adjusted RR, 0.87; 95% CI, 0.75-1.01) and during the intervention period (adjusted RR, 0.86; 95% CI, 0.74-1.00). CONCLUSION AND RELEVANCE: In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available, daily use of a MNP with iron did not result in an increased incidence of malaria among young children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01001871.

A systematic review of the application and utility of geographical information systems for exploring disease-disease relationships in paediatric global health research: the case of anaemia and malaria.

Malaria and anaemia are important health problems among children globally. Iron deficiency anaemia may offer protection against malaria infection and iron supplementation may increase the risk of malaria-related hospitalization and mortality. The nature and mechanism of these relationships, however, remain largely unresolved, resulting in concern and uncertainty around policies for non-selective iron supplementation in malaria endemic areas. Use of geographical information systems (GIS) to investigate this disease-disease interaction could contribute important new information for developing safe and effective anaemia and malaria interventions. To assess the current state of knowledge we conducted a systematic review of peer-reviewed and grey literature. Our primary objective was to qualitatively assess the application and utility of geographical concepts or spatial analyses in paediatric global health research. The secondary objective was to identify geographical factors that may be associated with anaemia and malaria prevalence or incidence among children 0-5 years of age living in low- and middle-income countries. Evaluation tools for assessing the quality of geographical data could not be found in the peer-reviewed or grey literature, and thus adapted versions of the STROBE (Strengthening The Reporting of Observational Studies in Epidemiology) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods were used to create reporting, and overall evidence quality scoring systems. Among the 20 included studies, we found that both malaria and anaemia were more prevalent in rural communities compared to urban areas. Geographical factors associated with malaria prevalence included regional transmission stability, and proximity to a mosquito breeding area. The prevalence of anaemia tended to vary inversely with greater or poorer access to community services such as piped water. Techniques for investigating geographic relationships ranged from simple descriptive mapping of spatial distribution patterns, to more complex statistical models that incorporated environmental factors such as seasonal temperature and rain fall. Including GIS in paediatric global health research may be an effective approach to explore relationships between childhood diseases and contribute key evidence for safe implementation of anaemia control programs in malaria endemic areas. Further, GIS presentation of ecological health data could provide an efficient means of translating this knowledge to lay audiences.

Relative efficacy of micronutrient powders versus iron-folic acid tablets in controlling anemia in women in the second trimester of pregnancy.

BACKGROUND: Iron deficiency is a major cause of anemia and the most prevalent nutrient deficiency among pregnant women in developing countries. The use of iron and folic acid supplements to treat and prevent iron-deficiency anemia has limited effectiveness, mainly due to poor adherence. Home fortification with a micronutrient powder for pregnant women may be an effective and acceptable alternative to traditional drug models. OBJECTIVE: To determine whether home fortification with micronutrient powders is at least as efficacious as iron and folic acid tablets for improving hemoglobin concentration in pregnant women. METHODS: A cluster-randomized noninferiority trial was conducted in the rural subdistrict of Kaliganj in central Bangladesh. Pregnant women (gestational age 14-22 weeks, n=478), were recruited from 42 community-based Antenatal Care Centres. Each centre was randomly allocated to receive either a micronutrient powder (containing iron,folic acid, vitamin C, and zinc) or iron and folic acid tablets. Changes in hemoglobin from baseline were compared across groups using a linear mixed-effects regression model. RESULTS: At enrolment, the overall prevalence of anemia was 45% (n = 213/478). After the intervention period, the mean hemoglobin concentrations among women receiving the micronutrient powder were not inferior to those among women receiving tablets (109.5 ± 12.9 vs. 112.0 ± 11.2 g/L; 95% CI, -0.757 to 5.716). Adherence to the micronutrient powder was lower than adherence to tablets (57.5 ± 22.5% vs. 76.0 ± 13.7%; 95% CI, -22.39 to -12.94); however, in both groups, increased adherence was positively correlated with hemoglobin concentration. CONCLUSIONS: The micronutrient powder was at least as efficacious as the iron and folic acid tablets in controlling moderate to severe anemia during pregnancy.

A combination of pH-sensitive caplet coatings may be an effective noninvasive strategy to deliver bioactive substances, nutrients, or their precursors to the colon.

We hypothesize that bacterially synthesized nutrients in the large intestine may significantly influence the nutritional status of humans and, specifically, that of the colonocytes. In vivo research with human subjects in this area has been extremely limited because of the absence of a noninvasive means to quantitatively deliver test doses of nutrients, or their precursors, to the colon. The purpose of this study was to design and test the effectiveness of a pH-dependent coating in delivering intact placebo caplets to the large intestine. Barium sulphate caplet cores (19.1 mm x 9.7 mm) were coated with 2 different pH-dependent acrylic copolymer products, Eudragit L100 and S100, in either a 1:0 ratio (100% Eudragit L100) or 3:1 ratio (75% Eudragit L100 and 25% S100). The disintegration profile of each formulation was determined through in vitro testing, then caplets were sequentially administered to 10 healthy volunteers, and monitored in vivo via serial abdominal fluoroscopic images. Test caplets with the 3:1 coating formulation had a 40% higher colon-targeting specificity compared with the 1:0-coated caplets, and tended to begin disintegrating at a later time after administration (p = 0.09). The total time from administration to complete disintegration was also significantly longer for the 3:1-coated caplets (p = 0.003). These results suggest that barium sulphate caplets with a 3:1 acrylic copolymer coating formulation ratio (Eudragit L100 and S100) may be a suitable delivery system for quantifying the biosynthesis of nutrients in the human large intestine and measuring their absorption across the colonic epithelium.

Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow-up.

OBJECTIVES: Human milk (HM) is the optimal source of nutrition for premature infants; however, it is unclear whether HM alone is sufficient to meet their elevated nutritional requirements early after hospital discharge. We previously reported that premature infants (750-1800 g birth weight) fed HM containing extra nutrients for 12 weeks after discharge had dietary intakes closer to recommended levels and grew more rapidly than those fed HM alone. The objectives of the present article are to examine the impact of this intervention on bone mineralization, body composition, and HM use up to 1 year. Data are also presented on general developmental level at 18-month corrected age (CA). PATIENTS AND METHODS: At discharge, predominantly HM-fed infants were randomized to receive for 12 weeks either approximately half of their feedings containing a multinutrient fortifier (intervention, n=19) or all of their feedings as HM alone (control, n=20). RESULTS: Intervention infants remained longer (P<0.001) and had greater whole-body bone mineral content (P=0.02) until 12-month CA compared with controls. Intervention infants born less than or equal to 1250 g continued to have a larger mean head circumference throughout the first year of life (P<0.0001). Human milk feeding (mL.kg(-1).day(-1)) differed between groups at 6- (P=0.035), but not 12-month CA. No statistically significant differences were found between groups in the mental, motor, or behavior rating scale scores of the Bayley II at 18-month CA. CONCLUSIONS: Adding a multinutrient fortifier to HM provided to predominantly HM-fed premature infants early after discharge results in sustained differences in weight, length, and whole-body bone mineral content, and in smaller babies, head circumference for the first year of life.